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di Giancarlo Nicoli

Sangamo (Nasdaq: SGMO)

is focused on the research and commercial development of engineered DNA-binding proteins for the regulation of gene expression and for gene modification. The basis of our proprietary technology is the engineering of a naturally occurring class of transcription factors, zinc finger DNA-binding proteins (ZFPs). When linked to functional domains that normally activate or repress gene expression, we create ZFP transcription factors (ZFP TFs) capable of turning genes on or off. ZFPs can also be linked to nuclease domains to create zinc finger nucleases (ZFNs) which enable precise gene-editing operations in cells. Engineered ZFNs can modify a cell’s DNA at a preselected location facilitating correction or disruption of a specific gene or the targeted addition of new DNA sequence.

In other words, with zinc finger proteins, SGMO is able to open any DNA strand in any precise location and add, cut, exchange genes.

There are other methods to do so, some of them are open source, but ZFP is the most precise and quickest.

A note on T Cells

T cells are like the cornerstone of the immune system. Remove them and the system breaks down. Normal people have over 500E6 (which means 500,000,000) of these cells in every liter of their blood. When HIV infects these cells they eventually die, leading to lower T cell counts. Less than 500E6 cells/L and you have AIDS, less that 200E6 cells/L and you’re pretty much done for. Without these cells to attack infections and keep them at bay you end up being a walking buffet table for microorganisms to eat.

How HIV attacks T cells

So after lots and lots of biology, it was shown that those T cells that are CD4+ (which means they express the CD4 protein on their surface) and also are CCR5+ (they have the CCR5 protein on their surface) can be infected by HIV. Without either receptor HIV doesn’t infect the T cell.

Why some people get exposed to HIV and don’t develop AIDS?

Take 10,000 (a statistically significant number) of normal people and give them all HIV. Yes that’s right, give them each an injection of a unique isolate of HIV. Then wait 10 years and see what happens.

No, no ethical review board on the earth would allow this experiment. But I tell you, this experiment has been done… in reverse.

Remember all of those poor transfusion patients who became HIV positive before labs started screening the blood supply? They were our 10,000. Though unintentionally infected with HIV through a contaminated blood supply, we can nonetheless look at their fate and find out what happened to them and in turn use those results to find the needle in the haystack. The overwhelming majority are either sick with AIDS or dead from AIDS. These poor unfortunate souls serve an important function for our genetics experiment. They are our positive control, they make us sure that when you infect people with HIV they get sick and then die. Which is very important to have if you’re looking to find things that stop them from getting sick and dying. But the numbers didn’t add up to 10,000. There was another class of people, those who never got sick.

When you give blood the Red Cross reserves some of it forever in a freezer so you can go back to it years later to check it out. So when researchers went back to the blood that was used in the transfusions they could tell where and when the people were infected with HIV. Most importantly we still have a sample of the blood. So each of the people infected but who never came down with symptoms of AIDS can have the HIV in the original blood sample tested.

There are people who we know for a fact were infected but never came down with the disease and have no HIV in their bodies, and the HIV isolated from the frozen blood sample was completely normal. Only one conclusion is possible from this, that these people are somehow resistant to HIV, but how?

Many people have a genetic defect, called the CCR5 delta-32 deletion. This defect prevents CD4 T cells from developing a receptor, called CCR5, on their surfaces. People who inherit this genetic mutation from both parents have CD4 T cells that lack the CCR5 entirely and, as a result, are highly resistant to infection with HIV.

Above three paragraphs almost entirely courtesy by Adenylyl.

The Berlinese Patient

The Berlinese Patient (here is the first reporthere is his coming forward) is a 40-year-old American HIV-positive man living in Berlin with a relapse of acute myeloid leukemia—a potentially fatal cancer of the immune system—in February 2007. Doctors performed a transplant that would increase the patient’s chance of cancer survival.

About 13 months after receiving the transplant, the patient’s leukemia relapsed yet again. Another transplant was performed. This led to a complete remission of the cancer.

The patient has regrown a new immune system after receiving those stem cell transplants and has since kept his viral load undetectable. In fact, sensitive tests have been unable to detect the virus in the patient’s blood or tissues. He is still HIV-free.

Point is, according to a report, presented by Berlinese Patient’s doctors (Gero Hütter, MD, of the Medical University of Berlin and his colleagues), the key to the transplant’s success was the stem cells provided by a donor whose immune system was genetically resistant to HIV infection. Yes, a donor with the CCR5 delta-32 deletion.

A quote from Berlin Patient Follow-Up ‘Strongly Suggests’ HIV Cure

“In summary,” the authors write, “our results demonstrate successful CD4+ T cell reconstitution at the systemic level as well as in the [gut] following [transplantation], and additionally provide evidence for the reduction in the size of the potential HIV reservoir overtime. Although the recovered CD4+ T cells are susceptible to infection with X4 HIV infection, the patient remains without any evidence for HIV infection since more than 3.5 years after discontinuation of ART. From these results, it is reasonable to conclude that cure of HIV infection has been achieved in this patient.”

Back to SGMO

Sangamo is using its ZFN-mediated gene disruption technology to disrupt the CCR5 gene in cells of a patient’s immune system to make these cells permanently resistant to HIV infection.  The aim is to provide a population of HIV-resistant cells that can fight opportunistic infections. In collaboration with scientists at the University of Pennsylvania and the University of Los Angeles California, UCLA, Sangamo is pursuing both ex- and in vivo approaches in T-cells and hematopoietic stem cells. In June 2008, Sangamo published the positive preclincal data from this program generated in a mouse model of HIV infection (Nat Biotechnol. 2008 Jul;26(7):808-16). In 2009, Sangamo initiated two Phase 1 clinical trials to evaluate our ZFP Therapeutic SB-728-T in T-cells for the treatment of HIV/AIDS.

First human clinical data of SB-728-T treatment of HIV/AIDS to be presented at a major medical conference. There will be four oral presentations on Sangamo’s HIV/AIDS programs at the 18th Conference on Retroviruses and Opportunistic Infections (CROI; February 27 – March 2, 2011; Boston). The acceptance of four oral presentations at a major medical conference despite being early in development suggests high interest among the medical community. The oral presentations will include interim data (safety, CD4 T-cell counts and levels of CCR5-modified T-cells) from two Phase 1 trials of SB-728-T treatment as well as data related to SB-728-HSC and the preclinical CXCR4 program.

Summing it up

I hope you did get it already. Anyway, summing it up: Sangamo possibly has at hand a cure against HIV/AIDS.

SGMO market cap as of friday’s close is $334M. What if HIV/AIDS treatment works? A ten bagger? Naaah! More than that imo obviously.

CROI is from Feb 27 to Mar 2, 2011. We’ll soon know more.

Phil Vardena’s stats:

ahrahr (99.05)

ahrahr lost to the market on Friday

Rank: 691 out of 72685

With SGMO, I’m down -30.09% since I selected it with CAPS, against a S&P +2.91%. My CAPS loss is -33.00.

Disclosure. I’m long the stock: SGMO.
This post is not intended to be investment advice of any kind. YMMV. Do your own DD.
Again, this is NOT investment advice.
This is NOT analysis, which is something six-figure equity research types do as full-time jobs for brokerage firms.
This is blogging. I just do like to share ideas.
And, past performance is not indicative of future results.

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